MADRID, SPAIN (UroToday.com) - In this talk, Dr. Christopher Sweeney reviewed the CHAARTED trial and discussed its results in comparison to the similar GETUG-15 trial performed in France. The CHAARTED trial compared the use of docetaxel in addition to androgen deprivation therapy (ADT) to ADT alone in patients with hormone-sensitive prostate cancer.

The rationale for the use of chemotherapy in addition to ADT came from the observation that patients with high metastatic burden have poorer outcomes with ADT alone when compared to those with low disease burden. One initial difficulty with the CHAARTED trial was establishing a definition for what constituted “high-volume disease.” Ultimately using a combination of previous classifications, the authors of the trial defined “high-volume disease” as any visceral metastases and/or 4 or more bone metastases, with at least one outside of the pelvis/vertebrae. He noted that at the start of the CHAARTED trial only patients with high-volume disease were recruited.

Dr. Sweeney then outlined the trial design. Patients in the docetaxel + ADT arm received 6 cycles of chemotherapy only. Only 6 cycles were used as this is the standard amount given for most solid tumors and it was felt that more doses would increase toxicity without adding benefit. Patients were stratified in each arm by age, extent of metastatic disease, ECOG performance status, and receipt of complete androgen blockade, prior ADT, and agents preventing skeletal-related events. The primary endpoint of the study was overall survival, with secondary endpoints including time to progressive disease, rates of PSA < 0.2ng/ml, and patient quality of life.

The study accrued 790 men between July 2006 and November 2012. The median age for the cohort was 64 years, the majority of patients were Caucasian, and the vast majority had an ECOG performance status of 0-1. Two-thirds of the patients in both arms had high-volume disease which Dr. Sweeney pointed out is a product of the bias of the type of patient that is typically referred to medical oncology in the hormone-naïve setting.

The trial found that use of docetaxel with ADT resulted in a significant improvement in overall survival. Median overall survival for the ADT + docetaxel arm was 57.6 months compared to 44 months for the ADT alone arm. The bulk of this survival difference was attributable to the high-volume disease patients. When analyzed separately, high-volume disease patients demonstrated a 17-month improvement in overall survival with ADT + docetaxel (49 mo. vs 32 mo. with ADT alone). In men with low-volume metastatic disease, the median survival for each arm has not been reached and more time is needed before any conclusions about the efficacy of the addition of docetaxel to ADT in this setting can be made.

With regards to secondary endpoints, significantly more patients in the ADT + docetaxel arm had a PSA < 0.2ng/ml at 6 and 12 months, and median time to castration-resistant prostate cancer (CRPC) and progression was prolonged. After progression, 75% of patients in the ADT-only arm received late docetaxel. The remainder received abiraterone, enzalutamide, or cabazitaxel.

Dr. Sweeney noted that 87.5% of patients were able to complete all 6 cycles of docetaxel, and 74% of patients did so without dose modifications. Toxicities included allergic reactions (3%), neuropathy (2%), diarrhea (1%), and fatigue (4%). Febrile neutropenia occurred in 6%. There was one death attributable to docetaxel.

Dr. Sweeney then focused on comparing the CHAARTED trial to the GETUG-15 trial. GETUG-15 was performed in France, and looked at the same two experimental arms as the CHAARTED trial. GETUG-15 in contrast, however, failed to demonstrate a difference in survival between the two arms. Dr. Sweeney pointed out that there were many similarities between the 2 trials including median overall survival of the 2 arms (ADT + docetaxel 58 mo. vs 61 mo. in CHAARTED and GETUG-15, respectively; ADT alone 44 mo. vs. 46 mo). Median age was similar, as was performance status distribution. Dr. Sweeney noted that differences between the 2 trials included fewer patients accrued in GETUG-15 (385 vs. 790 in CHAARTED), and more chemotherapy administered in GETUG-15 (8 cycles vs. 6 in CHAARTED).

While the initial report of GETUG-15 was a negative result, an updated analysis of GETUG-15 was presented at this year’s ASCU GU Symposium with longer follow up. Using the “high-volume disease” definition utilized in CHAARTED, improved survival was seen within the ADT + docetaxel arm with longer follow up (HR 0.8). This was not statistically significant but some separation of the survival curves could be seen. Dr. Sweeney stated that the differences in the trial results may be a product of the time period in which the studies were accrued. GETUG-15 accrual occurred earlier and thus there were fewer treatment options available for patients once they progressed to CRPC. Patients in the ADT + docetaxel arm received a significantly higher number of life-prolonging treatments in the CHAARTED trial compared to GETUG-15 which could help to account for a larger divergence of the survival curves in the CHAARTED trial.

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